When a mouse's immune system is deciding whether to reject a skin graft, one powerful member of a molecular family designed to provoke such a response can effectively reduce the visibility of the mouse's own cells and help the graft survive, researchers say.
"This is a molecule with huge potential to regulate immune response," Dr. Anatolij Horuzsko, reproductive immunologist at the Medical College of Georgia Center for Molecular Chaperone/Radiobiology and Cancer Virology, says of HLA-G dimer.
Dimer appears to be the most powerful among several known forms of HLA-G at inhibiting the immune response, researchers have found. Fetuses use this natural mechanism to hide from the mother's immune system and it's at work in some transplant patients as well.
Now that the scientists know which HLA-G is best at down-regulating the immune response and how it works, they believe the molecule's action can be augmented in people with organ transplants and autoimmune disease and turned down to help fight a tumor. Measuring endogenous levels of HLA-G dimer may also help physicians identify which transplant patients require little, if any, immune suppression.
Research published online in Proceedings of the National Academy of Sciences details that when HLA-G dimer binds with its inhibitory receptor, ILT4, it triggers a signaling pathway in which immune molecules IL-6 and STAT3 play a major role. "Biologically this is an interaction that requires several important suppressive molecules," says Dr. Horuzsko, the study's corresponding author and a faculty member in the MCG Schools of Medicine and Graduate Studies.
They looked at the resulting strong signaling in culture, then measured its impact on skin graft survival in mice and found it prolonged survival. Now Dr. Horuzsko is working with Dr. Laura Mulloy, chief of the Section of Nephrology, Hypertension and Transplantation Medicine in the MCG School of Medicine, to see if th
|Contact: Toni Baker|
Medical College of Georgia